Serum levels of complement C4 fragments correlate with disease activity in multiple sclerosis: Proteomic analysis

The aim of this study was to provide further insight into the effective contribution of classical soluble HLA-A, B and C class Ia (sHLA-I) and non-classical soluble HLA-G class Ib (sHLA-G) molecules in immune dysregulation occurring in multiple sclerosis (MS). We evaluated by enzyme-linked immunosorbent assay (ELISA) technique intrathecal synthesis and cerebrospinal fluid (CSF) and serum levels of sHLA-I and sHLA-G in 69 relapsing-remitting (RR), 21 secondary progressive (SP) and 13 primary progressive (PP) MS patients stratified according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also tested, as neurological controls, 91 patients with other inflammatory neurological disorders (OIND) and 92 with non-inflammatory neurological disorders (NIND). Eighty-two healthy volunteers served as further controls for sHLA-I and sHLA-G determinations. An intrathecal production of sHLA-I and sHLA-G detected by specific indexes was significantly more frequent in MS patients than in controls (p<0.01). An intrathecal synthesis of sHLA-I was prevalent in clinically (p<0.02) and MRI active (p<0.001) MS, whereas a CSF-restricted release of sHLA-G predominated in clinically (p<0.01) and MRI stable (p<0.001) MS. sHLA-I levels were low in the serum of clinically active (p<0.001) and high in the CSF of MRI active (p<0.01) MS. Conversely, sHLA-G concentrations were decreased in the serum of clinically stable MS (p<0.01) and increased in the CSF of MRI inactive MS (p<0.001). The trends towards a negative correlation observed between CSF and serum concentrations and intrathecal synthesis of sHLA-I and sHLA-G in patients without evidence of clinical and MRI activity confirmed that intrathecal production and fluctuations in CSF and serum concentrations of sHLA-I and sHLA-G were reciprocal in MS. Our results suggest that, in MS, a balance between classical sHLA-I and non-classical sHLA-G products modulating both MRI and clinical disease activity in opposite directions may exist.

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Soluble MHC class I chain-related protein B serum levels correlate with disease activity in relapsing–remitting multiple sclerosis

Human Immunology ◽

10.1016/j.humimm.2008.01.021 ◽

2008 ◽

Vol 69 (4-5) ◽

pp. 235-240 ◽

Cited By ~ 20

Author(s):

Juan Luís Fernández-Morera ◽

Sandra Rodríguez-Rodero ◽

Carlos Lahoz ◽

Alberto Tuñon ◽

Aurora Astudillo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Mhc Class I ◽

Serum Levels ◽

Class I ◽

Related Protein ◽

Relapsing Remitting ◽

Remitting Multiple Sclerosis ◽

Relapsing Remitting Multiple Sclerosis ◽

Protein B

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First trimester interleukin 8 levels are associated with postpartum relapse in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458509107009 ◽

2009 ◽

Vol 15 (11) ◽

pp. 1356-1358 ◽

Cited By ~ 18

Author(s):

Rinze F Neuteboom ◽

Evert Verbraak ◽

Jane SA Voerman ◽

Marjan van Meurs ◽

Eric AP Steegers ◽

...

Keyword(s):

Multiple Sclerosis ◽

High Risk ◽

Disease Activity ◽

Serum Levels ◽

First Trimester ◽

Interleukin 8 ◽

Disease Course ◽

Third Trimester ◽

The Third

Pregnancy has an ameliorating effect on multiple sclerosis (MS), but directly after delivery the risk of a relapse is increased. The pro-inflammatory chemokine interleukin 8 is associated with disease activity. We aimed to investigate whether pregnancy-induced fluctuations of interleukin 8 correlate with periods of enhanced and diminished disease activity. Thirty-six women with MS were prospectively studied before, during and after pregnancy. Serum levels of interleukin 8 were significantly decreased during the third trimester (p = 0.03). High first trimester serum levels of interleukin 8 were associated with a high risk of postpartum relapse (p = 0.007). These results help us to further understand the altered disease course during pregnancy.

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Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1191/135248506ms1274oa ◽

2006 ◽

Vol 12 (3) ◽

pp. 294-301 ◽

Cited By ~ 84

Author(s):

E Fainardi ◽

M Castellazzi ◽

T Bellini ◽

M C Manfrinato ◽

E Baldi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Matrix Metalloproteinase ◽

Disease Activity ◽

Neurological Disorders ◽

Serum Levels ◽

Matrix Metalloproteinase 9 ◽

Active Matrix ◽

Magnetic Resonance Imaging Mri ◽

Metalloproteinase 9

In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND ( P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS ( P<0.01) and OIND ( P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND ( P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical ( P<0.001, <0.001 and <0.05, respectively) and MRI ( P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity ( P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.

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Seasonal variations of 25-OH vitamin D serum levels are associated with clinical disease activity in multiple sclerosis patients

Journal of the Neurological Sciences ◽

10.1016/j.jns.2017.01.059 ◽

2017 ◽

Vol 375 ◽

pp. 160-164 ◽

Cited By ~ 14

Author(s):

Christina Hartl ◽

Viola Obermeier ◽

Lisa Ann Gerdes ◽

Mathias Brügel ◽

Rüdiger von Kries ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Disease Activity ◽

Seasonal Variations ◽

Serum Levels ◽

Clinical Disease ◽

Clinical Disease Activity ◽

25 Oh Vitamin D ◽

Multiple Sclerosis Patients

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Changes in serum levels of ICAM and TNF-R correlate with disease activity in multiple sclerosis

Neurology ◽

10.1212/wnl.53.4.758 ◽

1999 ◽

Vol 53 (4) ◽

pp. 758-758 ◽

Cited By ~ 31

Author(s):

S. J. Khoury ◽

E. J. Orav ◽

C. R. G. Guttmann ◽

R. Kikinis ◽

F. A. Jolesz ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Serum Levels

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TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458514560925 ◽

2015 ◽

Vol 21 (9) ◽

pp. 1121-1130 ◽

Cited By ~ 15

Author(s):

Alessandro Trentini ◽

Maria C Manfrinato ◽

Massimiliano Castellazzi ◽

Carmine Tamborino ◽

Gloria Roversi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Matrix Metalloproteinase ◽

Disease Activity ◽

Serum Levels ◽

Matrix Metalloproteinase 9 ◽

Relapsing Remitting ◽

Magnetic Resonance Imaging Mri ◽

Specific Tissue ◽

Metalloproteinase 9 ◽

Ms Pathogenesis

Background: The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown. Objective: To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis. Methods: We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing–remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls. Results: Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND ( p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients ( p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS ( p < 0.01 and p < 0.05, respectively). Conclusion: Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity.

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